Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity

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Sequence length dependence in arginine/phenylalanine oligopeptides : Implications for self-assembly and cytotoxicity. / Silva, Emerson R.; Listik, Eduardo; Han, Sang W.; Alves, Wendel A.; Soares, Bruna M.; Reza, Mehedi; Ruokolainen, Janne; Hamley, Ian W.

In: Biophysical Chemistry, Vol. 233, 01.02.2018, p. 1-12.

Research output: Contribution to journalArticleScientificpeer-review

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Silva, E. R., Listik, E., Han, S. W., Alves, W. A., Soares, B. M., Reza, M., ... Hamley, I. W. (2018). Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity. Biophysical Chemistry, 233, 1-12. https://doi.org/10.1016/j.bpc.2017.11.005

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Silva, Emerson R. ; Listik, Eduardo ; Han, Sang W. ; Alves, Wendel A. ; Soares, Bruna M. ; Reza, Mehedi ; Ruokolainen, Janne ; Hamley, Ian W. / Sequence length dependence in arginine/phenylalanine oligopeptides : Implications for self-assembly and cytotoxicity. In: Biophysical Chemistry. 2018 ; Vol. 233. pp. 1-12.

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@article{473f7ec71bb6422bae23cfd1deff127b,
title = "Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity",
abstract = "We present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form [RF]n (n = 1–5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of [RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-β structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of [RF]n peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self-assemblies rich in cationic groups when interacting with cell membranes.",
keywords = "Cross-β structure, Cytotoxicity, Fiber diffraction, Fibrillization, Scattering",
author = "Silva, {Emerson R.} and Eduardo Listik and Han, {Sang W.} and Alves, {Wendel A.} and Soares, {Bruna M.} and Mehedi Reza and Janne Ruokolainen and Hamley, {Ian W.}",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.bpc.2017.11.005",
language = "English",
volume = "233",
pages = "1--12",
journal = "Biophysical Chemistry",
issn = "0301-4622",
publisher = "Elsevier",

}

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TY - JOUR

T1 - Sequence length dependence in arginine/phenylalanine oligopeptides

T2 - Implications for self-assembly and cytotoxicity

AU - Silva, Emerson R.

AU - Listik, Eduardo

AU - Han, Sang W.

AU - Alves, Wendel A.

AU - Soares, Bruna M.

AU - Reza, Mehedi

AU - Ruokolainen, Janne

AU - Hamley, Ian W.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - We present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form [RF]n (n = 1–5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of [RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-β structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of [RF]n peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self-assemblies rich in cationic groups when interacting with cell membranes.

AB - We present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form [RF]n (n = 1–5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of [RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-β structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of [RF]n peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self-assemblies rich in cationic groups when interacting with cell membranes.

KW - Cross-β structure

KW - Cytotoxicity

KW - Fiber diffraction

KW - Fibrillization

KW - Scattering

UR - http://www.scopus.com/inward/record.url?scp=85036659308&partnerID=8YFLogxK

U2 - 10.1016/j.bpc.2017.11.005

DO - 10.1016/j.bpc.2017.11.005

M3 - Article

VL - 233

SP - 1

EP - 12

JO - Biophysical Chemistry

JF - Biophysical Chemistry

SN - 0301-4622

ER -

ID: 16609266